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时间:2019-02-26
《奥替拉西钾血药和尿药浓度的测定及其药代动力学和药物蓄积性评价》由会员上传分享,免费在线阅读,更多相关内容在行业资料-天天文库。
1、Seediscussions,stats,andauthorprofilesforthispublicationat:https://www.researchgate.net/publication/288272027DeterminationofpotassiumoxonateinhumanplasmaandurineanditspharmacokineticsandaccumulationevaluationinhumanArticleinJournalofChinaPharmaceuticalUniversity
2、·October2011CITATIONSREADS3776authors,including:HeZhuJiangsuProvinceAcademyofTraditionalChineseMedicine,Nanjing,China29PUBLICATIONS186CITATIONSSEEPROFILEAllcontentfollowingthispagewasuploadedbyHeZhuon18January2017.Theuserhasrequestedenhancementofthedownloadedfil
3、e.学报436JournalofChinaPharmaceuticalUniversity2011,42(5):436-442奥替拉西钾血药和尿药浓度的测定及其药代动力学和药物蓄积性评价*储妍,丁黎,刘荷英,于勇,朱贺,孙鲁宁(中国药科大学药物分析教研室,南京210009)摘要本实验建立了人血浆及尿液中奥替拉西钾(potassiumoxonate,Oxo)的LC-MS/MS测定方法,研究单次及多次给药替吉奥胶囊(S-1)后,Oxo在晚期胃癌患者体内的药代动力学特征,并评价多次给药后Oxo在人体内的药物蓄积情况。12名晚
4、期胃癌患者分别按体表面积(BSA)口服S-1:单次给药,受试者于早餐后给药60mg;多次给药,连续28d,每天2次,222于早餐后给药60mg;晚餐后给药60mg(BSA≥1.5m)或40mg(1.25m<BSA<1.5m)。采用LC-MS/MS法分别测定血浆及尿液中Oxo药物浓度,计算其药代动力学参数,评价其药代动力学特征和药物蓄积现象。血浆及尿液中Oxo测定的线性范围为分别为2~400ng/mL,0.02~10μg/mL。单次给药后cmax为(110.5±100.8)ng/mL,t1/2为(3.4±1.4)h,tm
5、ax为(2.2±0.7)h,36h内有(1.7±1.2)%的Oxo以原型方式从尿中排出;多次给药后,稳态平均血药浓度css-av为(36.89±29.35)ng/mL,稳态血药浓度波动度(DF)为2.4±0.8,经统计分析,多次给药28d后Oxo在胃癌患者体内药代动力学特征与单次给药相比并未发生变化,多次给药后未产生药物蓄积现象。与文献数据对照,Oxo在中国晚期胃癌患者与国外患者体内的药代动力学参数基本一致。关键词奥替拉西钾;药代动力学;药物蓄积评价;固相萃取;LC-MS/MS;替吉奥胶囊中图分类号R917;R969.
6、1文献标识码A文章编号1000-5048(2011)05-0436-07Determinationofpotassiumoxonateinhumanplasmaandurineanditsphar-macokineticsandaccumulationevaluationinhuman*CHUYan,DINGLi,LIUHe-ying,YUYong,ZHUHe,SUNLu-ningDepartmentofPharmaceuticalAnalysis,ChinaPharmaceuticalUniversity,Nanji
7、ng210009,ChinaAbstractAnLC-MS/MSmethodwasestablishedforthedeterminationofpotassiumoxonate(Oxo)inhumanplasmaandurine,thepharmacokineticsofOxowasinvestigatedinadvancedgastriccancerpatientsaftersingleandmultipleadministrationoftegafur,gimeracilandoteracilpotassiumc
8、apsule(S-1),andthesituationofdrugaccumulationaftermultipleadministrationwasevaluated.Formultipleadministration,12gastriccancerpatientsweretreatedwithS-1accordingtothe
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